Remarkable advances have been made in the care of post-operative and post-injury patients. Because of improvements in the care of acutely injured persons as well as advances in providing organ-specific supportive care, a new class of patients has been created. These patients represent the chronically critically ill. Multiple Organ Dysfunction Syndrome (MODS), defined by having two or more failing organ systems, is the clinical syndrome characteristic of these patients.
MODS is the leading cause of mortality in ICU patients. MODS represents the sequential deterioration of organ function, usually leading to death, occurring in patients who are on the most advanced ICU life support technology possible. These patients require considerable human and hospital resources, including invasive monitoring in an ICU, one-on-one nursing, multiple transfusions, ventilators, dialysis, cardiac assist devices, vasopressors and more. They are the sickest patients in a hospital, and they generally die with MODS.
At present, there is no active treatment that has proven successful for patients with MODS. Over the last three decades, tremendous advances have been made in improving the acute care of critically ill patients by providing organ specific supportive care. However, mortality in patients who survive the initial injury or insult and develop MODS remains unchanged. Extensive basic scientific research has indicated that it is the human host response to a severe physiological insult (e.g. car accident, major surgery, major infection, etc.) that is responsible for the development of progressive organ failure. A dysregulated and overwhelming host response, comprised of many intertwined endocrine, metabolic, neurologic, immune and inflammatory processes, is more complex than, but is analogous to an auto-immune reaction.
Following an exponential growth in the understanding of basic cellular and molecular mechanisms involved in this alteration in host response, numerous attempts at immunomodulation to treat this overwhelming response have been attempted. In over 30 randomized, controlled trials to treat patients with severe infection leading to organ dysfunction, despite compelling supportive laboratory experiments, all attempts at active treatment through immunomodulation have failed. Thus, active treatment of patients with MODS has eluded surgeons and intensivists who care for these patients.
Some of the most important tools used in coronary care units and intensive care units (ICU) are patient monitoring systems. These systems typically use sensors such as electrocardiogram sensors, temperature sensors and blood pressure sensors to measure physiological patient parameters. These patient parameters are then displayed on paper strip charts or video displays at a bedside unit or remotely at a nurse's station. Numerous advances have been made in monitoring systems to provide alarms and improve displays.
Traditional research, has focused on the endocrine, metabolic, cellular and molecular mechanisms involved in the human host response. Current traditional research also tests the efficacy of immunomodulation with clinical trials, where a benefit is evaluated for large cohorts of patients.
Evaluation of variability of patient parameters has only recently come under investigation in medical science, and is generally not used in routine clinical practice. Variability describes the degree to which a parameter fluctuates over time. It is a principal component of the dynamics of a variable, which refers to its pattern of change over time. A parameter may be relatively constant, demonstrating a low degree of variability, or wildly fluctuate with high variability.
The evaluation of heart rate variability has proven to contain valuable information regarding the cardiovascular status of a patient. It can provide accurate and reliable prognostic stratification of mortality risk following myocardial infarction or in patients with heart failure (Kleiger R E et al, American Journal or Cardiology 1987; 59:256 and Odemuyiwa O, et al, American Journal of Cardiology 1991; 68:434). Also, experimental human endotoxin administration will diminish heart rate variability (Godin P J et al, Critical Care Medicine 1996; 24:1117). Thus, diminished heart rate variability is correlated with pathologic alteration of the cardiovascular system.
In addition, evaluation of respiratory impedance variability in healthy controls and patients with asthma revealed increased variability in patients with asthma (Macklem P T, Annals RCPSC 1998, 31:194).
Thus, both increased and decreased variability of individual patient parameters are associated with disease states. The positive clinical significance of the evaluation of these individual variables indicates that the evaluation of multiple patient parameters will provide for clinically useful information. To date, there has been no attempt to provide clinicians with variability analysis of multiple patient parameters simultaneously, nor provide the capability for continuous real-time variability analysis and display.
Further discussion of complex non-linear systems and MODS may also be found elsewhere (A J E Seely, N V Christou, Critical Care Medicine, 28:2193, July 2000).
An example of the state of the art respecting physiological parameter monitoring is U.S. Pat. No. 5,438,983, issued Aug. 8, 1995 to Falcone. Falcone discloses alarm detection using trend vector analysis to provide improved alarm detection. Measured parameters are processed and possibly displayed. A safe zone is determined for these measured parameters and a trend vector is calculated for any measured values falling outside the safe zone. The trend vector can be shown on a display as an arrow indicating a direction and a length that indicates the magnitude of change in the parameter values.
Falcone therefore, gives an indication of the general direction in which a specific parameter is tending when it's values are in a range of values of concern and can provide alarms.
Another example of the state of the art respecting variability monitoring is U.S. Pat. No. 5,917,415, which issued Jun. 29, 1999 to Atlas. The patent teaches a wrist worn device and method for monitoring and alerting the user of increased drowsiness. The device includes sensors for monitoring several physiological parameters of the user, including peripheral pulse rate variability, peripheral vasomotor response, muscle tone, peripheral blood flow and reaction time variability. If the majority of these parameters are indicative of increased drowsiness, the audio-visual alert is provided the user. The sensors are encased in a shock-absorbing unit and wirelessly transmit the sensed data. Atlas monitors a plurality of non-medical parameters to predict a level of drowsiness useful in determining when a driver is no longer alert enough to operate a motor vehicle. The teachings of Atlas cannot be profitably applied to active therapeutic intervention.
In AN ARTICLE ENTITLED AN IMPROVED METHOD FOR MEASURING HEART-RATE VARIABILITY: ASSESSMENT OF CARDIAC AUTONOMIC FUNCTION published in BIOMETRICS 40,855-861, September 1984, Weinberg et al. describe how heart rate oscillates in synchrony with respiration. They proposed an easily computed measure,” the static R″, which is relatively resistant to the major non-respiratory sources of variation, including premature beats, heart-rate differences among subjects, and slow trends in heart rate over time within subjects. The method can also be used more generally in any context where individuals associate with event processes (for example, with seizures) , when one requires assessment of the extent to which the point process is periodic within a particular known period. The technique is applicable in any context where individual are associated with point processes, such as seizures where it is desirable to assess an extent to which, for a given individuals, the process is periodic with the particular known period, typically a daily or yearly cycle.
Unfortunately, current monitoring systems including that of Falcone, and Weinberg et al. do not provide sufficient prospective evaluation and analysis to identify and quantify changes to the systemic host response, necessary to perform active therapeutic intervention with MODS.
There therefore exists a need for a method and system for evaluating critically ill patients in order to facilitate modulation of the host response.